ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1267_1276dup (p.Gly426fs)

dbSNP: rs1967149532
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001047736 SCV001211716 pathogenic RYR1-related disorder 2022-09-01 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 844796). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This sequence change creates a premature translational stop signal (p.Gly426Glufs*82) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 20583297, 20839240, 23919265, 28818389).
GeneDx RCV002462280 SCV002757020 pathogenic not provided 2022-11-14 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV004004788 SCV004820742 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-04-10 criteria provided, single submitter clinical testing This variant inserts 10 nucleotides in exon 13 of the RYR1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product.This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar Variation ID: 844796). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RYR1 function due to haploinsufficiency is not an established disease mechanism for autosomal dominant malignant hyperthermia. Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

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